title: Induction of experimental autoimmune encephalomyelitis with recombinant human myelin oligodendrocyte glycoprotein in incomplete Freund's adjuvant in three non-human primate species.
abstract: The experimental autoimmune encephalitis (EAE) model is used for preclinical research into the pathogenesis of multiple sclerosis (MS), mostly in inbred, specific pathogen free (SPF)-raised laboratory mice. However, the naive state of the laboratory mouse immune system is considered a major hurdle in the translation of principles from the EAE model to the MS patient. Non-human primates (NHP) have an immune system harboring T- and B-cell memory against environmental antigens, similar as in humans. We sought to further refine existing NHP EAE models, which may help to bridge the gab between mouse EAE models and MS. We report here on new EAE models in three NHP species: rhesus monkeys (Macaca mulatta), cynomolgus monkeys (Macaca fascicularis) and common marmosets (Callithrix jacchus). EAE was induced with recombinant human myelin oligodendrocyte glycoprotein extracellular domain (1-125) (rhMOG) formulated in incomplete Freund's adjuvant (IFA). IFA lacks the bacterial antigens that are present in complete Freund's adjuvant (CFA), which are notorious for the induction of discomforting side effects. Clinically evident EAE could be induced in two out of five rhesus monkeys, six out of six cynomolgus monkeys and six out of six common marmosets. In each of these species, the presence of an early, high anti-rhMOG IgM response is correlated with EAE with an earlier onset and more severe disease course. Animals without an early high IgM response either did not develop disease (rhesus monkeys) or developed only mild signs of neurological deficit (marmoset and cynomolgus monkeys).
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH, Rijswijk, The Netherlands.
authors.forename: Krista G
authors.initials: KG
authors.lastname: Haanstra
authors.forename: S Anwar
authors.initials: SA
authors.lastname: Jagessar
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Bauchet
authors.forename: Mireille
authors.initials: M
authors.lastname: Doussau
authors.forename: Claire-Maëlle
authors.initials: CM
authors.lastname: Fovet
authors.forename: Nicole
authors.initials: N
authors.lastname: Heijmans
authors.forename: Sam O
authors.initials: SO
authors.lastname: Hofman
authors.forename: Jennifer
authors.initials: J
authors.lastname: van Lubeek-Veth
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Bajramovic
authors.forename: Yolanda S
authors.initials: YS
authors.lastname: Kap
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Hélène
authors.initials: H
authors.lastname: Touin
authors.forename: Laurent
authors.initials: L
authors.lastname: Watroba
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: François
authors.initials: F
authors.lastname: Lachapelle
authors.forename: Che
authors.initials: C
authors.lastname: Serguera
authors.forename: Bert A
authors.initials: BA
authors.lastname: 't Hart
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000473:pathology; D002144:Callithrix; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005620:Freund's Adjuvant / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008253:Macaca mulatta; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013116:Spinal Cord / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D007075:Immunoglobulin M; C571326:MOG protein, human; D063308:Myelin-Oligodendrocyte Glycoprotein; D011994:Recombinant Proteins; D005620:Freund's Adjuvant